prasugrel
thienopyridine P2Y12 receptor antagonist· Brands: EffientPO
Mechanism of action
Prasugrel is a thienopyridine prodrug that irreversibly blocks the P2Y12 subtype of ADP receptors on the platelet surface. This prevents ADP-mediated activation and glycoprotein IIb/IIIa receptor binding, inhibiting platelet aggregation for the lifetime of the platelet.
Pharmacokinetics
Prasugrel is rapidly absorbed after oral administration and hydrolysed to an intermediate, which is converted to the active metabolite by CYP3A and CYP2B6. The active metabolite reaches peak plasma concentration about 30 minutes after dosing, with an elimination half-life of approximately 3 to 4 hours. Platelet inhibition is dose-related and persists for the platelet lifespan. Excretion is mainly via the urine and faeces.
Indications & dosing
Acute coronary syndrome with percutaneous coronary intervention (loading dose)
Administered as a single loading dose at the time of PCI.
- adult · PO: 60 mg single dose · Administered as a single loading dose at the time of PCI.
Acute coronary syndrome with percutaneous coronary intervention (maintenance)
Continue for at least 12 months, or as recommended by current guidelines.
- adult · PO: 10 mg once daily · Continue for at least 12 months, or as recommended by current guidelines.
Acute coronary syndrome with PCI in patients weighing less than 60 kg or aged 75 years or older (maintenance)
Recommended maintenance dose in these patients.
- adult · PO: 5 mg once daily · Recommended maintenance dose in these patients.
Contraindications & precautions
- Active pathological bleeding (e.g., peptic ulcer, intracranial haemorrhage) · Prasugrel increases bleeding risk; any active bleeding is a contraindication.
- History of stroke or transient ischaemic attack (TIA) · Risk of major bleeding is increased in patients with prior stroke/TIA.
- Severe hepatic impairment · Prasugrel has not been studied in this population; avoid use.
- Hypersensitivity to prasugrel or any excipient · Cross-sensitivity with other thienopyridines may occur.
- Use with caution in patients aged 75 years or older; not recommended unless the patient has a high risk of thrombosis.
- Reduce dose to 5 mg once daily in patients weighing less than 60 kg.
- Consider withholding prasugrel 7 days before elective surgery due to increased bleeding risk.
- Caution in patients with moderate hepatic impairment or renal impairment.
- Avoid concomitant use with anticoagulants (e.g., warfarin, dabigatran) or NSAIDs due to increased bleeding risk.
- Consider CYP2C19 genotype status? (Prasugrel is less affected than clopidogrel, but no routine testing recommended.)
Adverse effects
- Bleeding (including bruising, epistaxis, gastrointestinal haemorrhage)serious
- Intracranial haemorrhageserious
- Thrombotic thrombocytopenic purpura (TTP)serious
- Diarrhoea
- Rash
- Allergic reactions (including angioedema)serious
Interactions
- aspirinmajorUse dual antiplatelet therapy only when clearly indicated, such as acute coronary syndrome or drug-eluting stent placement. Monitor for signs of bleeding, including occult blood loss. Consider gastroprotection with a proton pump inhibitor where appropriate. The duration of dual therapy should be guided by current cardiology guidelines and individual thrombotic versus bleeding risk.
Renal & hepatic adjustment
- eGFR 0+: No dose adjustment required. Caution in severe renal impairment due to limited clinical data.
- Hepatic impairment (severe): Contraindicated in severe hepatic impairment (Child-Pugh class C). (avoid)
- Hepatic impairment (moderate): No dose adjustment required in moderate hepatic impairment (Child-Pugh class B), but use with caution.
Monitoring, pregnancy & toxicity
- Signs and symptoms of bleeding (e.g. bruising, melaena, haematuria, intracranial haemorrhage) · Assess regularly during treatment
- Platelet count · Before and periodically during treatment, especially if bleeding occurs
- Haemoglobin · Before and periodically during treatment
- Pregnancy: Prasugrel is not recommended during pregnancy. No adequate human data; animal studies indicate potential risk to the fetus. Use only if clearly necessary and the potential benefit outweighs the risk to the fetus.
- Toxicity: Bleeding (e.g. gastrointestinal, intracranial, epistaxis, bruising) · Stop prasugrel. Provide supportive care. Platelet transfusion may be considered for severe bleeding, remembering that the effect of prasugrel persists for 7-10 days and transfused platelets may be affected if given too soon after a dose.
- Toxicity: Thrombotic thrombocytopenic purpura (TTP) · Rare but serious. Stop prasugrel and initiate plasma exchange. Manage in consultation with a haematologist.
Clinical notes
Prasugrel is indicated for the prevention of atherothrombotic events in patients with acute coronary syndromes undergoing percutaneous coronary intervention. It is given as a loading dose of 60 mg followed by a 10 mg maintenance dose once daily; a 5 mg maintenance dose is recommended for patients weighing less than 60 kg. Because of an increased bleeding risk, it is contraindicated in patients with a history of stroke or transient ischaemic attack, active bleeding, or severe hepatic impairment. Caution is advised in the elderly and in those with renal impairment.
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BNF; local formulary